Human prostatic membranes have been shown to contain what appears to be a classic membrane receptor for the plasma protein, sex hormone-binding globulin (SHBG, testosterone-estradiol-binding globulin). Further, the membrane-bound adenylate cyclase is activated when a small fraction of these receptors are occupied. Since the discovery of this receptor is so new, relatively little is known about it, or the consequences of its interactions with SHBG. The receptor will be purified to homogeneity from human prostatic membranes obtained at the time of transurethral prostatectomy for benign prostatic hypertrophy. The isolated receptor will be characterized as to its mol wt and subunit structure, and the kinetics of its interaction with SHBG will be examined. The binding domain of the receptor will be isolated by cross-linking it to [125-I]SHBG, submitting the cross-linked complex to tryptic digestion, and then isolating the complex by HPLC. The purified receptor also will be used as an antigen to obtain monoclonal and polyclonal antibodies. An estrogen responsive cell line (MCF-7) and an androgen responsive one (LNCaP), will be used as models to probe the biologic effects of SHBG, which has been prebound either to estradiol or testosterone. In these models, growth, overall protein secretion, the synthesis of specific proteins, the induction of adenylate cyclase activity, and receptor internalization will be evaluated. Finally, these cell lines will be used to establish whether the internalization of SHBG results in the concomitant internalization of steroids which are bound to it. SHBG binds estrogens and androgens with high affinity. The demonstration that receptors for the complex exist, and that important events occur after binding, opens new avenues to our understanding of both the normal physiology and the pathophysiology of the sex hormones.